Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose
Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose
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DOI：
10.1038/s41551-018-0293-z
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发表时间：
2019-02-01
影响因子：
28.1
通讯作者：
Wu, Xiaoyang
中科院分区：
文献类型：
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作者：
Li, Yuanyuan;Kong, Qingyao;Wu, Xiaoyang
可卡因成瘾与强迫性药物寻求有关，接触毒品或与毒品有关的线索会导致复发，即使在长时间戒除后也是如此。已经探索了各种药理学靶点和行为干预措施来对抗可卡因成瘾，但迄今为止还没有市场批准的治疗可卡因成瘾或复发的药物，并且缺乏对可卡因过量引起的急性紧急情况的有效干预措施。我们最近证明，皮肤表皮干细胞可以很容易地使用CRISPR进行编辑（聚集有规则间隔的短回文重复序列），然后移植回供体小鼠。在这里，我们展示了将皮肤细胞移植到小鼠体内，使其表达一种增强形式的丁基胆碱酯酶（一种水解可卡因的酶），使这种酶能够长期释放，并有效地保护小鼠免受可卡因寻求行为和可卡因过量的影响。通过皮肤移植诱发药物消除的皮肤基因治疗可能为解决药物滥用提供一种治疗选择。
Cocaine addiction is associated with compulsive drug seeking, and exposure to the drug or to drug-associated cues leads to relapse, even after long periods of abstention. A variety of pharmacological targets and behavioural interventions have been explored to counteract cocaine addiction, but to date no market-approved medications for treating cocaine addiction or relapse exist, and effective interventions for acute emergencies resulting from cocaine overdose are lacking. We recently demonstrated that skin epidermal stem cells can be readily edited using CRISPR (clustered regularly interspaced short palindromic repeats) and then transplanted back into the donor mice. Here, we show that the transplantation, into mice, of skin cells modified to express an enhanced form of butyrylcholinesterase-an enzyme that hydrolyses cocaine-enables the long-term release of the enzyme and efficiently protects the mice from cocaine-seeking behaviour and cocaine overdose. Cutaneous gene therapy through skin transplants that elicit drug elimination may offer a therapeutic option to address drug abuse.